The prevalence of Substance Use Disorder (SUD) is increasing along with the need to develop approaches to reduce the harm associated with substance use, including investigating alternatives such as cannabinoids, which show promising results, although the current evidence is limited. This scoping review focuses on the limitations and potentials of cannabinoid-based treatments for SUDs.
Methods:
We examined between-subject randomized controlled trials (RCTs) investigating the use of CBD and THC as pharmacological treatment for SUDs in adults, with the procedures attending the expectations of the Preferred Reporting Items for Scoping reviews and Meta-Analyses (PRISMA) for Scoping Reviews guidelines and assessed risk of bias using the Cochrane Risk of Bias Assessment Tool 2.
Results:
Ten RCTs were included, with six demonstrating low risk of bias, and positive results were found for treating Cannabis Use Disorder, while contradictory results were found for Opioid Use Disorder, and inconclusive results for treating Cocaine Use Disorder.
Conclusions:
CBD and THC demonstrate potential for treating some SUDs, but evidence is limited. Robust RCTs with larger samples and longer follow-up periods are necessary to assess carefully developed outcomes for different SUD patients. New cannabinoid-based medications and scientific-based policies may advance SUD treatment. A comprehensive approach to treatment and careful methodological choices may benefit patients with SUD.
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References
1.
American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders. Fifth Edition. American Psychiatric Association: Arlington, VA; 2013; doi: 10.1176/appi.books.9780890425596
ShermanBJ, SofisMJ, BorodovskyJT, et al.Evaluating cannabis use risk reduction as an alternative clinical outcome for cannabis use disorder. Psychol Addict Behav, 2022; 36(5):505–514; doi: 10.1037/adb0000760
6.
VolkowND, WoodcockJ, ComptonWM, et al.Medication development in opioid addiction: Meaningful clinical end points. Sci Transl Med, 2018; 10(434):eaan2595; doi: 10.1126/scitranslmed.aan2595
7.
FreemanTP, HindochaC, GreenSF, et al.Medicinal use of cannabis based products and cannabinoids. BMJ, 2019; 365:l1141; doi: 10.1136/bmj.l1141
SloanME, GowinJL, RamchandaniVA, et al.The endocannabinoid system as a target for addiction treatment: Trials and tribulations. Neuropharmacology, 2017; 124:73–83; doi: 10.1016/j.neuropharm.2017.05.031
10.
RissoC, BonifaceS, SubbaramanMS, et al.Does cannabis complement or substitute alcohol consumption? A systematic review of human and animal studies. J Psychopharmacol (Oxf), 2020; 34(9):938–954; doi: 10.1177/0269881120919970
11.
Le FollB. Opioid-sparing effects of cannabinoids: Myth or reality?. Prog Neuropsychopharmacol Biol Psychiatry, 2021; 106:110065; doi: 10.1016/j.pnpbp.2020.110065
12.
BilbaoA, SpanagelR. Medical cannabinoids: A pharmacology-based systematic review and meta-analysis for all relevant medical indications. BMC Med, 2022; 20(1):259; doi: 10.1186/s12916-022-02459-1
MontoyaAK. Selecting a within- or between-subject design for mediation: Validity, causality, and statistical power. Multivariate Behav Res, 2022; 9:1–21; doi: 10.1080/00273171.2022.2077287
15.
NavarreteF, García-GutiérrezMS, GasparyanA, et al.Role of cannabidiol in the therapeutic intervention for substance use disorders. Front Pharmacol, 2021; 12:626010; doi: 10.3389/fphar.2021.626010
16.
TriccoAC, LillieE, ZarinW, et al.PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and explanation. Ann Intern Med, 2018; 169(7):467–473; doi: 10.7326/M18-0850
17.
PaulusV, BillieuxJ, AmineB, et al.Cannabidiol in the context of substance use disorder treatment: A systematic review. Addict Behav, 2022; 132:107360; doi: 10.1016/j.addbeh.2022.107360
18.
PageMJ, McKenzieJE, BossuytPM, et al.The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 2021; 372:n71; doi: 10.1136/bmj.n71
19.
MorganCJA, DasRK, JoyeA, et al.Cannabidiol reduces cigarette consumption in tobacco smokers: Preliminary findings. Addict Behav, 2013; 38(9):2433–2436; doi: 10.1016/j.addbeh.2013.03.011
20.
HindochaC, FreemanTP, GrabskiM, et al.Cannabidiol reverses attentional bias to cigarette cues in a human experimental model of tobacco withdrawal: Cannabidiol for tobacco withdrawal. Addiction, 2018; 113(9):1696–1705; doi: 10.1111/add.14243
21.
Siklos-WhillansJ, BacchusA, ManwellLA. A scoping review of the use of cannabis and its extracts as potential harm reduction strategies: Insights from preclinical and clinical research. Int J Ment Health Addict, 2021; 19(5):1527–1550; doi: 10.1007/s11469-020-00244-w
22.
SterneJAC, SavovićJ, PageMJ, et al.RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ, 2019; l4898; doi: 10.1136/bmj.l4898
23.
LevinFR, MarianiJJ, BrooksDJ, et al.Dronabinol for the treatment of cannabis dependence: A randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend, 2011; 116(1–3):142–150; doi: 10.1016/j.drugalcdep.2010.12.010
24.
LevinFR, MarianiJJ, PavlicovaM, et al.Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend, 2016; 159:53–60; doi: 10.1016/j.drugalcdep.2015.11.025
25.
AllsopDJ, CopelandJ, LintzerisN, et al.Nabiximols as an agonist replacement therapy during cannabis withdrawal: A randomized clinical trial. JAMA Psychiatry, 2014; 71(3):281–291; doi: 10.1001/jamapsychiatry.2013.3947
26.
LintzerisN, BhardwajA, MillsL, et al.Nabiximols for the treatment of cannabis dependence: A randomized clinical trial. JAMA Intern Med, 2019; 179(9):1242; doi: 10.1001/jamainternmed.2019.1993
27.
FreemanTP, HindochaC, BaioG, et al.Cannabidiol for the treatment of cannabis use disorder: A phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial. Lancet Psychiatry, 2020; 7(10):865–874; doi: 10.1016/S2215-0366(20)30290-X
28.
TrigoJM, SolimanA, QuiltyLC, et al.Nabiximols combined with motivational enhancement/cognitive behavioral therapy for the treatment of cannabis dependence: A pilot randomized clinical trial. PLoS One, 2018; 13(1):e0190768; doi: 10.1371/journal.pone.0190768
29.
BisagaA, SullivanMA, GlassA, et al.The effects of dronabinol during detoxification and the initiation of treatment with extended release naltrexone. Drug Alcohol Depend, 2015; 154:38–45; doi: 10.1016/j.drugalcdep.2015.05.013
30.
HurdYL, SpriggsS, AlishayevJ, et al.Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: A double-blind randomized placebo-controlled trial. Am J Psychiatry, 2019; 176(11):911–922; doi: 10.1176/appi.ajp.2019.18101191
31.
Mongeau-PérusseV, BrissetteS, BruneauJ, et al.Cannabidiol as a treatment for craving and relapse in individuals with cocaine use disorder: A randomized placebo-controlled trial. Addiction, 2021; 116(9):2431–2442; doi: 10.1111/add.15417
32.
de Meneses-GayaC, CrippaJA, HallakJE, et al.Cannabidiol for the treatment of crack-cocaine craving: An exploratory double-blind study. Braz J Psychiatry, 2021; 43(5):467–476; doi: 10.1590/1516-4446-2020-1416
33.
HaneyM, HartCL, VosburgSK, et al.Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology (Berl), 2008; 197(1):157–168; doi: 10.1007/s00213-007-1020-8
34.
TrigoJM, LagzdinsD, RehmJ, et al.Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings. Drug Alcohol Depend, 2016; 161:298–306; doi: 10.1016/j.drugalcdep.2016.02.020
35.
LintzerisN, MillsL, DunlopA, et al.Cannabis use in patients 3 months after ceasing nabiximols for the treatment of cannabis dependence: Results from a placebo-controlled randomised trial. Drug Alcohol Depend, 2020; 215:108220; doi: 10.1016/j.drugalcdep.2020.108220
36.
MillsL, DunlopA, MontebelloM, et al.Correlates of treatment engagement and client outcomes: Results of a randomised controlled trial of nabiximols for the treatment of cannabis use disorder. Subst Abuse Treat Prev Policy, 2022; 17(1):67; doi: 10.1186/s13011-022-00493-z
37.
CrippaJAS, HallakJEC, Machado-de-SousaJP, et al.Cannabidiol for the treatment of cannabis withdrawal syndrome: A case report: CBD and cannabis withdrawal. J Clin Pharm Ther, 2013; 38(2):162–164; doi: 10.1111/jcpt.12018
38.
ShannonS, Opila-LehmanJ. Cannabidiol oil for decreasing addictive use of marijuana: A case report. Integr Med Encinitas Calif, 2015; 14(6):31–35.
39.
HindochaC, McClureEA. Unknown population-level harms of cannabis and tobacco co-use: If you don't measure it, you can't manage it. Addiction, 2021; 116(7):1622–1630; doi: 10.1111/add.15290
40.
HindochaC, FreemanTP, FerrisJA, et al.No smoke without tobacco: A global overview of cannabis and tobacco routes of administration and their association with intention to quit. Front Psychiatry, 2016; 7:104; doi: 10.3389/fpsyt.2016.00104
41.
LakeS, St. Pierre M. The relationship between cannabis use and patient outcomes in medication-based treatment of opioid use disorder: A systematic review. Clin Psychol Rev, 2020; 82:101939; doi: 10.1016/j.cpr.2020.101939
42.
LakeS, WalshZ, KerrT, et al.Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis. PLoS Med, 2019; 16(11):e1002967; doi: 10.1371/journal.pmed.1002967
43.
MeachamMC, NoblesAL, TompkinsDA, et al.“I got a bunch of weed to help me through the withdrawals”: Naturalistic cannabis use reported in online opioid and opioid recovery community discussion forums. PLoS One, 2022; 17(2):e0263583; doi: 10.1371/journal.pone.0263583
44.
SocíasME, ChoiJ, LakeS, et al.Cannabis use is associated with reduced risk of exposure to fentanyl among people on opioid agonist therapy during a community-wide overdose crisis. Drug Alcohol Depend, 2021; 219:108420; doi: 10.1016/j.drugalcdep.2020.108420
45.
HurdYL, YoonM, ManiniAF, et al.Early phase in the development of cannabidiol as a treatment for addiction: Opioid relapse takes initial center stage. Neurotherapeutics, 2015; 12(4):807–815; doi: 10.1007/s13311-015-0373-7
46.
ShannonS, LewisN, LeeH, et al.Cannabidiol in anxiety and sleep: A large case series. Perm J, 2019; 23(1):18–041; doi: 10.7812/TPP/18-041
47.
SouzaJDS, ZuardiAW, GuimarãesFS, et al.Maintained anxiolytic effects of cannabidiol after treatment discontinuation in healthcare workers during the COVID-19 pandemic. Front Pharmacol, 2022; 13:856846; doi: 10.3389/fphar.2022.856846
48.
FitzmauriceGM, LipsitzSR, WeissRD. Within-treatment frequency of use versus abstinence as a predictor of longitudinal post-treatment follow-up assessments of drug use. Drug Alcohol Depend, 2020; 208:107857; doi: 10.1016/j.drugalcdep.2020.107857
49.
LoflinMJE, KilukBD, HuestisMA, et al.The state of clinical outcome assessments for cannabis use disorder clinical trials: A review and research agenda. Drug Alcohol Depend, 2020; 212:107993; doi: 10.1016/j.drugalcdep.2020.107993
50.
Cannabis Policy Research Workgroup. Recommendations for NIDA's Cannabis Policy Research Agenda. National Institution of Drug Abuse (NIDA)—National Advisory Council on Drug Abuse Workgroup: Bethesda, MD; 2018.
51.
FeingoldD, FoxJ, RehmJ, et al.Natural outcome of cannabis use disorder: A 3-year longitudinal follow-up. Addiction, 2015; 110(12):1963–1974; doi: 10.1111/add.13071
52.
FeingoldD, HochE, WeinsteinA, et al.Editorial: Psychological aspects of cannabis use and cannabis use disorder. Front Psychiatry, 2021; 12:789197; doi: 10.3389/fpsyt.2021.789197
53.
LucasP, BoydS, MilloyM-J, et al.Reductions in alcohol use following medical cannabis initiation: Results from a large cross-sectional survey of medical cannabis patients in Canada. Int J Drug Policy, 2020; 86:102963; doi: 10.1016/j.drugpo.2020.102963
54.
LucasP, BoydS, MilloyM-J, et al.Cannabis significantly reduces the use of prescription opioids and improves quality of life in authorized patients: Results of a large prospective study. Pain Med, 2021; 22(3):727–739; doi: 10.1093/pm/pnaa396
55.
McClureEA, RabinRA, LeeDC, et al.Treatment implications associated with cannabis and tobacco co-use. Curr Addict Rep, 2020; 7(4):533–544; doi: 10.1007/s40429-020-00334-8
56.
Müller-VahlKR, JakubovskiE, FremerC, et al.Implications for blinding in clinical trials with THC-containing cannabinoids based on the CANNA-TICS trial. Front Neurosci, 2022; 16:793703.
57.
RussoEB. Current therapeutic cannabis controversies and clinical trial design issues. Front Pharmacol, 2016; 7:309; doi: 10.3389/fphar.2016.00309
58.
WilseyB, DeutschR, MarcotteTD. Maintenance of blinding in clinical trials and the implications for studying analgesia using cannabinoids. Cannabis Cannabinoid Res, 2016; 1(1):139–148; doi: 10.1089/can.2016.0016
59.
JichaCJ, LofwallMR, NuzzoPA, et al.Safety of oral dronabinol during opioid withdrawal in humans. Drug Alcohol Depend, 2015; 157:179–183; doi: 10.1016/j.drugalcdep.2015.09.031
60.
LofwallMR, BabalonisS, NuzzoPA, et al.Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans. Drug Alcohol Depend, 2016; 164:143–150; doi: 10.1016/j.drugalcdep.2016.05.002
61.
DyerO. Opioid lawsuits: Sackler family agree final $6bn civil settlement with US states. BMJ, 2022; 376:o616; doi: 10.1136/bmj.o616
62.
EvansWN, LieberEMJ, PowerP. How the reformulation of OxyContin ignited the heroin epidemic. Rev Econ Stat, 2019; 101(1):1–15; doi: 10.1162/rest_a_00755
63.
PowellD, PaculaRL. The evolving consequences of OxyContin reformulation on drug overdoses. Am J Health Econ, 2021; 7(1):41–67; doi: 10.1086/711723
64.
LinLA, BohnertASB, BlowFC, et al.Polysubstance use and association with opioid use disorder treatment in the US Veterans Health Administration. Addiction, 2021; 116(1):96–104; doi: 10.1111/add.15116
65.
MarsSG, BourgoisP, KarandinosG, et al.“Every ‘never’ I ever said came true”: Transitions from opioid pills to heroin injecting. Int J Drug Policy, 2014; 25(2):257–266; doi: 10.1016/j.drugpo.2013.10.004
66.
LakeS, KerrT, BuxtonJ, et al.The cannabis-dependent relationship between methadone treatment dose and illicit opioid use in a community-based cohort of people who use drugs. Cannabis Cannabinoid Res, 2023; 8(1):155–165; doi: 10.1089/can.2021.0080
67.
MokJ, MilloyMJ, GrantC, et al.Use of cannabis as a harm reduction strategy among people who use drugs: A cohort study. Cannabis Cannabinoid Res, 2022; doi: 10.1089/can.2021.0229. PMID: 35647886.
68.
de AlmeidaRBF, SantosNTV, de BritoAM, et al.The use of “virado” as a harm reduction strategy among crack users in the State of Pernambuco, Brazil. Salud Colect, 2020; 16:e2528; doi: 10.18294/sc.2020.2528
69.
FlemingT, BarkerA, IvsinsA, et al.Stimulant safe supply: A potential opportunity to respond to the overdose epidemic. Harm Reduct J, 2020; 17(1):6; doi: 10.1186/s12954-019-0351-1
70.
KilukBD, BabuscioTA, NichC, et al.Smokers versus snorters: Do treatment outcomes differ according to route of cocaine administration?. Exp Clin Psychopharmacol, 2013; 21(6):490–498; doi: 10.1037/a0034173
71.
LiuY, RichardsVL, GebruNM, et al.Associations amongst form of cocaine used (powder vs crack vs both) and HIV-related outcomes. Addict Behav Rep, 2021; 14:100374; doi: 10.1016/j.abrep.2021.100374
72.
ChavesTV, SanchezZM, RibeiroLA, et al.Crack cocaine craving: Behaviors and coping strategies among current and former users. Rev Saúde Pública, 2011; 45:1168–1175; doi: 10.1590/S0034-89102011005000066
73.
BastosADA, AlbertiS. From the psychosocial paradigm to religious morality: ethical issues in mental health [In Portuguese]. Ciênc Saúde Coletiva, 2021; 26:285–295; doi: 10.1590/1413-81232020261.25732018
74.
National Inspection Report on Therapeutic Communities—2017 [In Portuguese]. 1st ed. Mecanismo Nacional de Prevenção e Combate à Tortura: Brasília, DF, Brasil; 2018.
75.
NunesMO, de LimaJM, PortugalCM, et al.Psychiatric reform and counter-reform: An analysis of a socio-political and sanitary crisis at national and regional level [In Portuguese]. Ciênc Saúde Coletiva, 2019; 24:4489–4498; doi: 10.1590/1413-812320182412.25252019
76.
Miró Ò, DarganPI, WoodDM, et al.Epidemiology, clinical features and management of patients presenting to European emergency departments with acute cocaine toxicity: Comparison between powder cocaine and crack cocaine cases. Clin Toxicol, 2019; 57(8):718–726; doi: 10.1080/15563650.2018.1549735. PMID: 30696283.
77.
PerrenoudLO, OikawaKF, WilliamsAV, et al.Factors associated with crack-cocaine early initiation: A Brazilian multicenter study. BMC Public Health, 2021; 21(1):781; doi: 10.1186/s12889-021-10769-x
78.
RibeiroA, PintoDGA, TrevisolAP, et al.Can contingency management solve the problem of adherence to antiretroviral therapy in drug-dependent individuals?. Health Educ Behav, 2023; doi: 10.1177/10901981221148966
79.
TardelliVS, BisagaA, TadonioL, et al.Evidence-based treatment for stimulant use disorder: Time to hit the community. Can J Psychiatry Rev Can Psychiatr, 2022; doi: 10.1177/07067437221148831. PMID: 36583534.
80.
ChaconFT, Raup-KonsavageWM, VranaKE, et al.Secondary terpenes in Cannabis sativa L.: Synthesis and synergy. Biomedicines, 2022; 10(12):3142; doi: 10.3390/biomedicines10123142
81.
FerberSG, NamdarD, Hen-ShovalD, et al.The “entourage effect”: Terpenes coupled with cannabinoids for the treatment of mood disorders and anxiety disorders. Curr Neuropharmacol, 2020; 18(2):87–96; doi: 10.2174/1570159X17666190903103923
82.
RussoEB. The case for the entourage effect and conventional breeding of clinical cannabis: No “strain,” no gain. Front Plant Sci, 2019; 9:1969; doi: 10.3389/fpls.2018.01969
RussoEB, GuyGW. A tale of two cannabinoids: The therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses, 2006; 66(2):234–246; doi: 10.1016/j.mehy.2005.08.026
86.
HillKP, GoldMS, NemeroffCB, et al.Risks and benefits of cannabis and cannabinoids in psychiatry. Am J Psychiatry, 2022; 179(2):98–109; doi: 10.1176/appi.ajp.2021.21030320
87.
KudrichC, HurdYL, SalsitzE, et al.Adjunctive management of opioid withdrawal with the nonopioid medication cannabidiol. Cannabis Cannabinoid Res, 2022; 7(5):569–581; doi: 10.1089/can.2021.0089
88.
RussoEB. When the pharmacopoeia fails: Cannabis for pain. Pain Med, 2023; doi: 10.1093/pm/pnac208. PMID: 36592031.
89.
BerlV, HurdYL, LipshutzBH, et al.A randomized, triple-blind, comparator-controlled parallel study investigating the pharmacokinetics of cannabidiol and tetrahydrocannabinol in a novel delivery system, Solutech, in association with cannabis use history. Cannabis Cannabinoid Res, 2022; 7(6):777–789; doi: 10.1089/can.2021.0176
90.
RussoEB, PlumbJ, WhiteleyVL. Novel solventless extraction technique to preserve cannabinoid and terpenoid profiles of fresh cannabis inflorescence. Molecules, 2021; 26(18):5496; doi: 10.3390/molecules26185496
91.
RussoEB, CuttlerC, CooperZD, et al.Survey of patients employing cannabigerol-predominant cannabis preparations: Perceived medical effects, adverse events, and withdrawal symptoms. Cannabis Cannabinoid Res, 2022; 7(5):706–716; doi: 10.1089/can.2021.0058
92.
FreemanTP, MehtaMA, NeillJC, et al.Restrictions on drugs with medical value: Moving beyond stalemate. J Psychopharmacol (Oxf), 2018; 32(10):1053–1055; doi: 10.1177/0269881118798609
93.
SayetteMA. The role of craving in substance use disorders: Theoretical and methodological issues. Annu Rev Clin Psychol, 2016; 12(1):407–433; doi: 10.1146/annurev-clinpsy-021815-093351
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